The majority of human neoplasms is thought to be due to environmental factors. There is overwhelming evidence that skin cancer, one of the most commonly occurring human cancers, is usually due to exogenous insult. Tumor promoters, such as 12-0-tetradecanoyl-phorbol-13-acetate (TPA), are very active in enhancing epidermal carcinogenesis in mouse skin but not in other species. The role of promoting agents in human neoplasms is unknown. The purpose of this work is (1) to develop an in vitro system consisting of hamster epidermal cells to study mechanisms of neoplastic transformation by environmental carcinogens and tumor promoters, (2) to determine the basis for the species specificity of tumor promoters, and (3) to determine if tumor promoters can induce mitotic aneuploidy.